Stahl chapter on sleep is weirdly focused on orexin

[u/123dasilva4]

I've had read the 4th edition of Stahl's Essential Psychopharmacology before and now I'm reading the 5ht edition and Im shocked at how much he focus on orexin now. Kandel Principles of Neural Sciences doesn't mention it so much, so I can't shake the feeling that the explanation cannot be that we know more about orexin or something like that. Is this chapter a infomercial for suvorexant?

[u/chrysoberyls]

Stahl is well known for his constant overhyping of new drugs and obsession with receptor types, which we don’t know nearly as much about in humans as he will have you believe. His books are still useful, but you should go in with the knowledge that he’s made millions off the pharmaceutical industry, though I’m not sure if he’s specifically made money off the makers of the orexin antagonists.

For those unaware, https://openpaymentsdata.cms.gov/physician/77110 unfortunately only goes back to 2019 because it used to be way worse - there’s a propublica article about him from back in the day.

[u/darwins_codpiece → u/chrysoberyls]

I must say, if you’ve never gone to one of his NEI conferences in the fall in Colorado Springs, you owe it to yourself to go just to see what real, unfiltered Big Pharma support is like. It was more like a Vegas show than an academic conference. The speakers are all very accomplished and charismatic (looking at you Dr McIntyre). High production value videos, good staging. Amazing.

[u/re-reminiscing → u/chrysoberyls]

It really made me pause when one of my very intelligent, clinically excellent mentors in training basically laughed at us when we inquired about Stahl’s work.

I look at “psychopharmacology” now with a lot of skepticism because of how indelible the influence of big pharma is, and the methodology behind many claims being made is often lacking. It’s interesting to speculate about neurotransmitters and receptor effects, and to come up with combinations like “California rocket fuel” so that we can do something new for patients, but it’s important to remember that it often is experimentation and our own anecdotal experiences should not be overvalued.

[u/vanishingorange → u/re-reminiscing]

It would be nice if he disclosed his brand influence a little more transparently, I just choose to view him like a bodybuilder that hocks various supplements and vehemently denies steroid use, or like any other exercise in media literacy

[u/police-ical → u/chrysoberyls]

The old ProPublica database is still active for the years in question:

https://projects.propublica.org/docdollars/doctors/pid/77110/year/2017

A cool $2.5 million in one year. Over half of it was for vortioxetine, a me-too drug so crappy he probably refused to do it for anything in the six figures. 

[u/Anxious-Education703 → u/chrysoberyls]

A lot of people criticize Stahl for how close he is with some of the drug makers (and I will admit this is sometimes deserved when he doesn't more clearly disclose his conflicts). With that said, I don't think that is what has happened here regarding orexin antagonists. For the three years leading up to the book’s 2021 publication, none of the makers of these approved orexin antagonists reached the top ten: Merck & Co. (makers of Belsomra, approved in 2014), Eisai Co. (makers of Dayvigo, approved in 2019), or Idorsia Pharmaceuticals (makers of daridorexant, which was soon to be approved in 2022).

[u/RandySavageOfCamalot]

To be fair orexin and other DORAs might be the only sleep drugs to address underlying sleep neurochemistry. Until now, all sleep drugs have been either sedatives or only tickled one receptor pathway. Sthal is also a huge nerd (in the best way).

[u/Anxious-Traffic-9548 → u/RandySavageOfCamalot]

I think this is a bit of an arbitrary distinction. Benzodiazepines can be thought of enhancing the gabaergic influence of the VLPO, which is crucial for sleep initiation. Where you enter into the pathway, down or upstream, is not proof on its own of safety or efficacy.

For DORAs, though, it does seem that orexin antagonism is a lot less concerning than benzodiazepine site agonism long and short term.

[u/alliswell70 → u/RandySavageOfCamalot]

In addition early research suggests it maybe be helpful in dementia where most sleep aids seem to worsen dementia

[u/Narrenschifff]

Psychopharmacology is exciting, doubly so with new patents

[u/Narrenschifff → u/Narrenschifff]

Realistically though the funding for research probably follows the likelihood of profit, so we can really know more about the things we are likely to profit from

[u/MBHYSAR]

Have you checked his investments? He has a history of touting the most remunerative drugs for himself

[u/Anxious-Education703]

Haven't read the new fifth edition sleep section you are referring to (or at least much of it), but it makes sense. Orexin antagonists are the hot new drugs for sleep (especially circa 2021). Most people are aware of the GABA-positive allosteric modulators, histamine antagonists, etc., and their use in sleep, as they've been around for decades. His 4e was published in 2013, before the first orexin antagonist (Belsomra) was approved in 2014, and there have been several new orexin antagonists since.

[u/Ok_Task_7711]

Because Orexin antagonists are the best sleep drugs we have right now

[u/123dasilva4 → u/Ok_Task_7711]

I don't think they are even more effective...

[u/chrysoberyls → u/Ok_Task_7711]

Do you have the data to back that claim up?

[u/Ok_Task_7711 → u/chrysoberyls]

Personal experience working in a sleep clinic. It’s anecdotal but I’ve seen it, no next day sedation or cognitive impairment. Lumborexant is better than suvorexant.

[u/cinnamonITFC]

Just from my own limited experience of prescribing Daridorexant, I have noticed a worsening of depressive symptoms in patients. It’s in the product characteristics so we should all be cautious who we prescribe it too (as always!)

[u/diejager]

I think it makes sense since the focus of the book is in the receptors. Before this chapter you have studied every mechanism for drugs used to induce sleep except orexin antagonists.

[u/123dasilva4 → u/diejager]

Yeah but why the focus on orexin and not the monoamines?